Tobacco smoke footprints mar placental landscape

As many as 20 percent of pregnant women continue to smoke, despite warnings that it can harm their developing fetuses. Their placentas reflect those dangers with markers of metabolic stress and oxidative damage caused by highly reactive molecules called free radicals, said researchers from Baylor College of Medicine and The University of Texas Medical Branch at Galveston in a report in the current issue of the American Journal of Obstetrics and Gynecology.

"Not only does this study help us understand the cellular and molecular damage caused by smoking, but it also reflects the problems caused by second-hand smoke and ambient exposures to other pollutants, which are laden with polycyclic aromatic hydrocarbons," said Dr. Kjersti Aagaard, assistant professor of obstetrics and gynecology at BCM and corresponding author of the report. Aromatic hydrocarbons are among the hazardous air pollutants monitored by environmental health agencies (as part of the Clean Air Act) and are thought to be involved in many chronic and acute health issues, including cancer and cardiovascular disease.

The placenta is a flat circular organ in the uterus that is absolutely essential to a healthy pregnancy, nourishing the developing fetus.

Detrimental effects of smoking

"This study builds on our previous work focused on the effects of smoking on pregnancy and particularly the molecular mechanisms behind the damage caused by maternal tobacco use in pregnancy," said Aagaard. "There are a number of detrimental effects from smoking in pregnancy and exposure to second-hand smoke."

Among these are growth restriction of the developing fetus, pre-term birth and placental abruption, a devastating occurrence when the placenta prematurely detaches from the uterus.

"There are a number of byproducts from smoking that seem to accumulate in the placenta," said Aagaard.

In her study, she and her colleagues collected placental tissue from a large cohort of women who smoked during pregnancy, and then examined them in great detail to compare their histology to nonsmokers. They studied the cellular changes within the placentas in detail, looking for indications of damage and specifically oxidative damage.

"We observed clear evidence of oxidative damage and stress," said Aagaard. One of these findings was an increased amount of syncytial knots in the placentas of smokers, consistent with oxidative stress and cellular damage, she said. High numbers of these knots are associated with chronic high blood pressure and stillbirth.

Smokers vs. nonsmokers

"These patterns were remarkably different between smokers and nonsmokers," said Aagaard. "When combined with our other published work, we are piecing together the genetic susceptibility, and cellular markers which suggests that maternal smoking leaves an epigenetic footprint and a metabolic stress footprint on the placenta." Epigenetics refers to chemical changes that affect the way genes operate.

"We are slowly unraveling how environmental exposures in pregnancy leave an indelible mark on the fetus and its pregnancy lifeline - the placenta. The bits and pieces of this story are coming together and will aid in future discoveries and potential interventions with implications beyond the level of 'just quit'," said Aagaard.

Others who took part in this work include Dr. Melissa A. Suter, Dr. Adi R. Abramovici, Dr. Lauren Patterson and Cynthia Shope, all of BCM; and Dr. Elena Sbrana, Joan E. Moss, and Dr. Hal K. Hawkins of UTMB.